Trends in Microbiology
ReviewVaccines to Overcome Antibiotic Resistance: The Challenge of Burkholderia cenocepacia
Section snippets
Antibiotic Resistance and Its Impact on CF
Bacterial multidrug resistance is a major challenge of our time: as recently described by the World Health Organization, it represents a global priority, and for some dangerous pathogens a standard eradication protocol is still lacking (https://www.who.int/antimicrobial-resistance/en/). In recent years many scientists have focused their research on CF patients who are at particular risk of infection by microorganisms resistant to several antibiotics [1]. CF is caused by deficiency in the CTFR
Microbial Communities in the CF Lung Environment
CF patients suffer from chronic lung infections caused by complex polymicrobial communities that are responsible for inflammation and a progressive decline in lung function (Figure 1, Key Figure). Culture-independent, next-generation sequencing-based studies revealed that known CF pathogens (Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, and multiple species of Haemophilus and Burkholderia cepacia complex) coexist with additional members of the CF lung community – such as
Why Is B. cenocepacia Difficult to Treat and Eradicate?
B. cenocepacia is one of the most clinically relevant members of the Bcc, a group of 24 closely related bacterial species [21], described for the first time by Walter Burkholder in 1949. B. cenocepacia is a ubiquitous nonglucose fermenter aerobic Gram-negative bacterium that is commonly isolated from water, soil, and from sputum of CF patients.
The incidence of B. cenocepacia infections in CF patients is only 3%, but this infection leads to a 2.5-fold reduction in their life expectancy relative
Immune Response
The characterization of the immune response to B. cenocepacia is extremely complex: CF patients have an abnormal immune regulation because bacteria are embedded in the mucin layer or in the intracellular environment, and this can interfere with the host immune response. The airway epithelium is overlaid by high molecular weight glycoproteins (mucins) that provide a physical barrier. In normal conditions, bacteria bind to the mucins and are cleared by the mucociliary activity. In CF patients,
The Challenge for the Future
In recent decades, advances in DNA sequencing technology and bioinformatics have produced an exponential growth of genome sequence data, thus accelerating the acquisition of knowledge on functional networks among bacterial genes and proteins, and providing new opportunities for vaccine development (Figure 1). The whole-genome sequences publicly available represent a valuable source of information in the search for novel vaccine candidates. Bioinformatic analysis of bacterial genomes can use a
Concluding Remarks and Future Perspectives
The success of these new technologies could open the way to the identification and modeling of Burkholderia antigens selected either by reverse vaccinology or through the isolation of monoclonal antibodies derived from immunized animals or isolated from infected patients that recognize key antigens (see Outstanding Questions). The new antigens could then be overexpressed in outer-membrane vesicles, which are known to act as an ideal delivery system for bacterial antigens, or be expressed in
Acknowledgments
This work was supported by a grant from the Cystic Fibrosis Foundation (RICCAR17G0 to G.R.), a BlueSky research grant of the University of Pavia (to S.B.), and funding from the Italian Ministry of Education, University, and Research (MIUR), Dipartimenti di Eccellenza Program (2018–2022), to the Department of Biology and Biotechnology 'L. Spallanzani', University of Pavia.
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These authors contributed equally